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Flashcards in CNS infections 1 Deck (75):
1

Most Common Agents of Congenital Infections

TOxoplasma,
Rubella,
Cytomegalovirus [CMV],
Herpes simplex virus [HSV]) -2 or -1

TORCH test: a series of tests for specific IgM in chord blood
(may be STORCH: syphilis)

one more: Lymphocytic choriomenigitis virus (LCMV)

2

HSV infections cause infection and morbidity in neonates:
areas ?

Skin, Eye, Mouth
CNS disease
Disseminated disease with or without CNS disease

3

the leading cause (by far) of infection and morbidity in the neonate

CMV
40,000 neonates born in US/yr affected-->sequelae (hearing loss, vision loss, and cognitive impairment) in 1/5th of cases

4

nosocomial-acquired meningitis orgs

*half of all meningitis cases in US

Gram-positive cocci:
Staphylococcus aureus
coagulase-negative staphylococci
non-pneumococcal streptococci

Gram-negative rods

5

Predisposing conditions for Nosocomial-acquired meningitis

recent neurological procedures.
presence of neurological devices.
altered immune status

6

??? is NOT a portal of entry for viral infection

the brain

Infection in the CNS is usually a secondary infection, occurring days, weeks, months, or years after the initial infection


7

bacterial meningitis vs. viral meningitis

less common

used to be more but now we vaccinate against mumps?

many not def. ddx
devastating sequelae

8

bac meningitis neonate orgs

Streptococcus agalactiae, Escherichia coli
K. pneumoniae

9

bac meningitis infant and young kiddo orgs

N. meningitides
S. pneumoniae
Myobacterium tuberculosis.

10

bac meningitis adolescents →Elderly orgs

N. meningitides
S. pneumoniae

>50-y-o: L. monocytogenes

11

The problem for the physician is to differentiate between bacterial pyogenic/purulent meningitis, which is a ?? and ?? viral meningitis

medical emergency

benign

12

Symptoms of bacterial meningitis in the older child → adult include acute onset of:

*irritability
*lethargy (altered mental status)
*fever
severe headache
nuchal rigidity
vomiting
opisthotonos
pressure on eyeball
photophobia

13

the single most important predisposing factor for meningitis in the neonate

Low birth weight

Low birth weight (LBW;

14

What factors predispose the LBW, VLBW, and ELBW infant to infection?

Impaired innate and adaptive immune functions

if Require nosocomial techniques and devices to keep alive

Incidence of sepsis is much higher

Maternally related events allow agent access to fetus before birth or during parturition

15

Impaired innate and adaptive immune functions

Antibodies production and PMN (both in number, function) are poor in newborn, especially in prematurely born infants

16

nosocomial techniques and devices

Are often kept in 80% humidity, an environment where bacteria & fungi flourish.
Presence of multiple invasive devices:
catheters
feeding tubes
suction tubes

17

Maternally related events allow agent access to fetus before birth or during parturition, such as

Premature rupture of membranes, esp. for greater than 24 hours.

Maternal infection during last week of pregnancy, e.g.,
vaginosis,
UTI
cervicitis
chorioamnionitis

Excessive manipulation during delivery

Use of intrauterine monitoring devices

18

Sources of etiologic agent:(neonate meningitis)

Infection acquired in utero (Common source):
From infected chorioamnionic and amniotic fluid.
From infected blood – via chord blood – transplacental transmission.

Infection during parturition, aspiration of infected vaginal secretions (Common source).

Infection acquired hours → days post-partum from caregiver(s).

19

Signs and symptoms of meningitis in the neonate are not the same as the adult and include:

Fever
Lethargy
Poor feeding
GI disturbance (vomiting/diarrhea)/abdominal distension
Respiratory abnormalities (e.g., dyspnea, cyanosis)
Cardiac abnormalities (tachycardia)
Bulging fontanelle

20

neonatal meningitis px

generally poor, mortality rates vary from 10-60% with survivors showing some permanent defects (neurological sequelae) which may be significant

21

Streptococcus agalactiae - Group B Streptococci (GBS):

Gram-positive cocci in chains or pairs (AKA streptococci).

β-hemolytic on sheep blood agar via production of the ornithine rhamnolipid pigment or lipid toxin.

Bacitracin-resistant versus GAS, which is bacitracin- sensitive

22

S. agalactiae group based on ??

cell wall antigen

Lancefield's serological classification based primarily on cell wall carbohydrate (C carbohydrate, teichoic acids). Groups A→T. Groups A, B, D are clinically important.

23

S. agalactiae also serologically typed based on ??

capsular polysaccharide:

Major virulence factor –

There are several (9) groups:

Five groups (especially Group III) are most common causes of both early and late onset disease.

24

S. agalactiae is the leading cause of ?? alone or with ?? within the first 3 months of life

bacteremia
meningitis and/or pneumonia as complications

Incidence is highest in pre-term, but most (75%) cases occur in full-term infants (more of those guys)

25

1/3 of all invasive GBS disease occurs in ??

pregnant women (Maternal UTI caused by GBS frequently occurs before or just after birth).

26

adults, esp. elderly can also get GBS

usually with chronic or immunosuppressive disease:

persons > 60 y-o-age is high (4 → 7 cases/100,000 population) with a high (25%) mortality rate.

Diabetes, cirrhosis, malignancy, AIDS.

*Clinical GBS syndromes occur in virtually all tissues/organs

27

GBS Transmission and Reservoir:

Vertical infection occurs before and/or during birth

Horizontal infection (mother/caregiver → newborn) occurs after birth.

Agent colonizes mother’s pharynx, vagina, and skin via rectal colonization:
-Not all gravid females are colonized by GBS.
-Not all gravid females colonized by GBS pass it to the neonate.
-Not all neonates carrying GBS become infected/diseased.

*no seasonality

28

Two forms of neonatal disease are recognized:

Early (acute) onset sepsis (bacteremia)

Late (insidious) onset sepsis (bacteremia or focal infection)

29

Early (acute) onset sepsis (bacteremia):

Occurs within the first 6 days after birth.

Source is mother, infection is acquired in utero or via passage through birth canal.

More common form of disease (80% of cases)

30

Late (insidious) onset sepsis (bacteremia or focal infection):

Occurs 7 days → 3 months following birth.

Source: associated with postpartum acquisition in the nursery (care givers) or community or mothers.

Focal infections include:
meningitis
cellulitis
osteomyelitis
septic arthritis.

Less common form of this disease (20% of cases)

31

Meningitis occurs in few (5%) cases of ?? but many (@30%) cases of ??

early onset sepsis

late onset sepsis

Because of the higher mortality rate and the occurrence of neurological sequelae associated with meningitis, have a high index of suspicion for meningitis

32

hemolytic GBS pigment triggers mast cell degranulation, resulting in the release of ??

mast cell degranulation in the lower genital tract can limit colonization of ??

preformed and proinflammatory mediators



hyperpigmented GBS strains

33

Isolation of GBS from:
the patient (i.e., neonate) from normally sterile sites:

CSF
blood
lungs

34

Isolation of GBS from: the mom

vagina.
nasopharynx.
GI tract/anus.
skin.

35

Identification of the organism:

Rapid slide agglutination to ID GBS, based on C-specific substance/carbohydrate.

other tests - PCR

36

The screening approach for GBS:

all pregnant mothers be screened at 35→37 weeks gestation (Studies show that this is best approach)

2 specimens are collected, swabs from rectum and vagina
all identified carriers and women who deliver pre-term before screening should be offered intrapartum antimicrobial prophylaxis iv

37

intrapartum antimicrobial prophylaxis iv (GBS)

Penicillin G
ampicillin

if penicillin-intolerant:
Cefazolin

Vancomycin if:
susceptibility to erythromycin and clindamycin has not been performed or has been found resistant

38

GBS: antibiotic prophylaxis before labor starts and single administration of postpartum antibiotic prophylaxis for newborns are ??

ineffective

39

There are no reports of resistance to ?? but GBS resistance to ?? and ?? has been reported at 15-30% and 10-20% of cases, respectively

penicillin G
erythromycin, clindamycin

40

The risk factors assessment (non screening)approach for GBS

intrapartum antimicrobial agents (same antibiotics as stated above administered iv) should be offered to any pregnant women with 1 or more of the following risk factors:

elevated intrapartum temperature
membrane rupture > 18 hours
premature onset of labor
premature rupture of membrane (PROM) at

41

Many (NOT ALL) hospitals have adopted the CDC recommendations or give all mothers antibiotics and this has resulted in ??

a BIG decrease in GBS infections in neonates in US

42

There is no prevention strategy for ??

late onset GBS disease

43

Problems with Intrapartum Antibiotic Exposure:

with increased use of intrapartum antibiotics to reduce the incidence of neonatal GBS infection, the incidence of early onset sepsis in VLBW infants has not changed, but the ??? have changed

etiologic agents responsible

e.g., E. coli are now the primary etiologic agents

therapy is resulting in an increased incidence of late onset sepsis

44

Listeria monocytogenes

A Gram positive, coccobacilli (rod), motile, coryneform species. (may look like cocci but are NOT)

Not fastidious.

Growth temperature range is broad (0→50o C). Isolated by cold enrichment, like Yersinia.


45

L. mono are IC or EC??

facultative intracellular pathogens

Invade & multiply in nonprofessional phagocytes: epithelial cells.
endothelial cells.

Survive and multiply within phagocytic cells such a:
non-activated macrophages and monocytes.
enterocytes.

46

Listeria is Serologically heterogeneous

Numerous serotypes based on O & H antigens

*Three serotypes account for most infections in animals and humans

47

Virulence factors of listeria

Lipoteichoic acids (LPS-rare for G+): Immunomodulator as potent

Proteins: enzymes required for organism-directed phagocytosis and cell-to-cell spread.

48

Listeria incidence

sporadic cases and food-borne epidemics.

49

Listeria Transmission and reservoirs

Food-borne: ingestion is primary mode, esp. adults, rare disease but mortality is high.

Human-to-human:
in utero - transplacental (vertical) transfer.
during parturition (vertical) transmission.

Animal-to-human; a zoonosis.

50

Primary reservoirs: Listeria

distributed worldwide – is ubiquitous:

soil
water
normal fecal flora of mammals - including humans: Human immune carriers exist.
food (tons!)

51

Age and gender and seasonality of Listeria

preggos
SUMMER: food assoc.

52

Listeria risk factors

Immunosuppression - T cell suppression: These are the populations for which you should have a high index of suspicion of listeriosis!:

young/neonates (3rd leading cause of invasive neonatal disease).

Aged/elderly persons: >70 y-o-age (2/100,000),

Pregnant females (12/100,000),

Advanced HIV/AIDS pt: (70→210/100,000),

Other: Immunosuppressive therapy (esp. T cell deficiencies)

Cancer
Diabetes

53

Incidnce of Listeria in the general population is ??


most cases due to ??

rare!



Sporadic disease
NOT common-source outbreaks

54

Listeria pathogenesis

Organism is ingested → passes through the intestinal epithelium → bacteremia

55

Listeria POE is the ??

GIT

Agent is phagocytized by gastrointestinal cells (without damaging the integrity of the GI tract) and macrophages (agent survives in non-activated macrophages). Concurrent/Intercurrent GITI with another pathogen may promote infection with Listeria?

56

?? induce phagocytosis of Listeria by nonprofessional phagocytic cells (similar to Shigella) and also mediate entry into epithelial cell

Surface proteins

57

Enzymes (esp. ??) disrupt the phagosome membrane allowing Listeria cells to escape from the host vacuole and replicate in the host cell cytoplasm

listeriolysin O

58

Cell-to-cell infection occurs when a tail of ?? form at the ends of the Listeria cells due to virulence factors, e.g., ??

Same mechanism is used by ??

polymerized actin filaments

ActA


Shigella sp., Rickettsia and vaccina virus

59

Listeria has a tropism for

CNS (meninges and brain, especially the brain-stem) and is capable of penetrating and infecting brain parenchyma (usually brain stem).

placenta.

60

Listeria incubation period

may be long (about 30 days; range is 11→70 days).

61

Listeria immunity

Primarily T cell-mediated immunity

control of infection requires activated macrophages, which can only kill *stationary (latent*) phase Listeria*
(better pathogen than Mtb!)

62

Listeria Infections in pregnancy: occurrence and manifestations

Illness usually occurs in the 3rd trimester, with the greatest decline in gravid female’s CMI.

Gravid female manifests with acute, febrile illness - severe flu-like symptoms due to bacteremia. Mother rarely manifests with CNS infection

63

Outcomes of Listeria Fetal (in utero) infection:



fetal mortality?

early-onset sepsis syndrome,
spontaneous abortion (from 5m gestation on),
stillborn,
premature births.

Fetal mortality rate is high (15→50%).

64

Listeria Early-onset sepsis syndrome:

is associated with prematurity.

Infection is likely acquired in utero via inhalation of infected amniotic fluid.

Agent is found in neonate practically everywhere (in the:
external ear
nose
throat
blood
CSF
*lungs
*gut

Symptoms manifest in newborn (

65

Listeria Granulomatosis infantisepticum is ??

agent found in ??

a rare condition involving in utero infection

disseminated abscess and/or granulomas in multiple internal organs, esp. liver & spleen.
papules in throat, skin may also be present.

Neonate mortality rate is high (>50%).

66

Listeria Late-onset meningoencephalitis

Infection occurs during or after birth.

Symptoms manifest in between 1→2 weeks postpartum.

Neonate mortality rate is moderate (10 → 20%).

Mother is asymptomatic.

67

Adults w/ Listeriosis manifest with one or more of:

Meningitis (acute or subacute)

Meningoencephalitis

Encephalitis

Macroscopic brain abscess (mass lesions) with meningitis:
Seizures can occur

*Listeria has tropism for brain (esp. brain stem).

Bacteremia may → flu-like disease. Predisposing factors as stated above.

Food poisoning/gastroenteritis

Focal non meningeal infections are uncommon

68

Listeria Food poisoning/gastroenteritis symptoms include:

occurs in who ??

fever
headache
arthropathy & myalgia
non-bloody diarrhea
abdominal cramps, nausea, vomiting

Occurs in both immunocompetent and immunocompromised persons

69

Listeria ddx: based on

etiologic agents based on population

70

Listeria dx: Cx

sedimented CSF.

amniotic fluid.

blood (esp if pt. spikes or has a fever).

tissues including placenta.

feces (if present, present in low numbers [20 CFU/g feces]) so prolonged, cold-enrichment may improve chances of isolation.

detection in food (must be same serotype as that isolated from patient to prove source).

71

Listeria dx: Gram stain

Sources:
sedimented CSF.
amniotic fluid.
blood (esp
feces.

72

Listeria dx: Gram stain limitations ??

morphology similar to either Corynebacterium sp. or coccobacilli.

easily decolorized (appear Gram-negative or not stained).

present in small numbers in feces, so easily missed

73

Listeria dx: CSF with listerial meningoencephalitis:

misdiagnosis??

monocytes predominate.
glucose level is often normal.

low probability of observing Listeria in CSF (

74

Listeria tx

ampicillin + gentamycin. Alternative is TMP-SMX

75

Listeria prevention

NONE

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